PROJECT SUMMARY This project is specifically responsive to the following aspects of the scope of the Centers for Oceans and Human Health 3: Impacts of Climate Change on Oceans and Great Lakes (COHH3) (P01): 1) determine impacts of climate change on increasing incidence of harmful algal bloom (HAB) events; (2) understand mechanisms of toxicity underlying health impacts linked to climate change; (3) address populations in US coastal and Great Lakes regions (e.g., those with existing health or social disparities) that will be more vulnerable to human health risks that are associated with or exacerbated by climate change. The goal of this project is to understand and quantify the impacts of exposure Vibrio species (V. vulnificus and V. parahaemolyticus) and increased toxin production in Cyanobacteria such as Microcystis aeruginosa. The effects of climate change are likely to increase the incidence of these microbes leading to potentially greater exposure through the food chain and via other exposure routes. Specifically, this Project will assess the effects of climate change-altered Vibrio bacteria and Microcystin toxin on mammalian model exposure systems individually and in combination. In addition, exposures will include microplastics, a major contaminant of emerging concern in coastal and aquatic ecosystems, correlated with increased urbanization, which is increasing as the effects of climate change are being felt. The effects of the mixture of these components will be investigated through appropriate experimental design and statistical analysis. Effects on critical organ systems (liver, kidney and gut), alterations in inflammation and increased disease states (non-alcoholic liver disease including human non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), along with and polycystic ovarian syndrome (PCOS)), will be quantified. We have preliminary data that shows the exposure of microcystins in rodent models of existing chronic nonalcoholic fatty liver disease exacerbate liver pathology leading to bridging fibrosis in both kidney and livers. We also found significant alterations in the gut microbiome following microcystin exposure that led to gut leaching and portal endotoxemia, a recipe for systemic inflammation and organ damage via pattern recognition receptors (TLRs and P2X7rs). In addition, microplastics can contain multiple endocrine disrupting chemicals and microcystins have recently been reported to exhibit endocrine disrupting effects, both of which potentially lead to reproductive dysfunctions. Lastly, effects of microplastics on seafood safety will be evaluated. The emerging role of microplastics, their consumption by bivalve molluscs (oysters), fish and other marine organisms and theuir ability to act as vectors for other pollutants such as the microcystin toxins, pose a serious threat to the human health, in particular owing to increasing reliance on these foods around the world. This Project clearly underpins two-way dialogue instigated within the Community Engagement Core, while there are also clear links with the Vibrio and Cyanobacteria Projects to produce bacteria and toxins with greater potency for toxicity testing. 1